Data from: Rituximab vs placebo induction prior to glatiramer acetate monotherapy in multiple sclerosis

Objective: To examine whether rituximab induction followed by glatiramer acetate (GA) monotherapy is more effective than GA alone for the treatment of relapsing MS with active disease. Methods: This was a single center, double-blind, placebo-controlled study(NCT01569451). Fifty-five participants were randomly assigned (1:1ratio) to either rituximab (R-GA) or placebo induction (P-GA), followed by all participants initiating GA therapy. Participants were followed up to 3-years. The primary endpoint was the number of participants with no evidence of disease activity (NEDA) (those without relapse, new MRI lesions and sustained change in disability. Results: Twenty-eight and 27 participants received rituximab and placebo induction, respectively, with one participant in each arm withdrawing prior to 6-month MRI. There were no significant differences in baseline characteristics. At end of study, 44.44% of R-GA participants demonstrated NEDA, vs 19.23% of P-GA participants (p = 0.049). A smaller proportion of R-GA participants failed treatment (37.04%R-GA vs 69.23%P-GA, p=0.019), and time to treatment failure was longer (23.32 monthsR-GA vs 11.29 monthsP-GA, p=0.027). Fewer participants in the R-GA arm had new lesions (25.93%R-GA vs 61.54%P-GA, p=0.009), and there were fewer new T2 lesions (0.48R-GA vs 1.96P-GA vs, p=0.027). Probability of demonstrating NEDA in the R-GA arm returned to baseline within the study period. There were no differences in adverse events. Conclusions: Induction therapy with rituximab followed by GA may provide superior efficacy in the short term to GA alone in relapsing MS, but this benefit appears to wane within the study period. Larger studies are needed to assess sustainability of results.

研究目标：探究先予利妥昔单抗（rituximab）诱导治疗后序贯醋酸格拉替雷（glatiramer acetate，GA）单药治疗，对比单纯GA单药治疗，用于活动性复发型多发性硬化（multiple sclerosis, MS）的疗效优劣。
研究方法：本研究为单中心、双盲、安慰剂对照试验（临床试验注册号：NCT01569451）。共纳入55名受试者，按1:1比例随机分配至利妥昔单抗诱导序贯GA治疗组（R-GA组）与安慰剂诱导序贯GA治疗组（P-GA组），后续所有受试者均启动GA治疗。随访时长长达3年。本研究的主要终点为达到无疾病活动证据（no evidence of disease activity, NEDA）的受试者人数，即无复发、无新发磁共振成像（magnetic resonance imaging, MRI）病灶且残疾状态无持续进展的受试者。
研究结果：分别有28名与27名受试者接受利妥昔单抗诱导治疗与安慰剂诱导治疗，两组各有1名受试者在6个月磁共振成像扫描前退出研究。两组受试者的基线特征无显著差异。研究结束时，R-GA组有44.44%的受试者达到NEDA，P-GA组该比例为19.23%（p=0.049）。R-GA组的治疗失败率更低（37.04% vs 69.23%，p=0.019），且至治疗失败的时间更长（23.32个月 vs 11.29个月，p=0.027）。R-GA组出现新发病灶的受试者比例更低（25.93% vs 61.54%，p=0.009），新发T2病灶数量也更少（0.48 vs 1.96，p=0.027）。在本研究周期内，R-GA组达到NEDA的概率回归至基线水平。两组的不良事件发生率无显著差异。
研究结论：先予利妥昔单抗诱导治疗后序贯GA治疗，相较于单纯GA单药治疗，可在短期内为复发型MS患者带来更优的疗效，但该获益在本研究周期内逐渐衰减。未来需开展更大样本量的研究以评估该研究结果的可持续性。